Diagnostic value of ProGRP for small cell lung cancer in different stages

Dong, Aoran; Zhang, Jiali; Chen, Xiaobin; Ren, Xiaoyan; Zhang, Xinwei

doi:10.21037/jtd.2019.04.29

Cited by 21 publications

(20 citation statements)

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“…ProGRP is the precursor protein of the bombesin‐like peptide, a neuropeptide and autocrine growth factor expressed in nerve fibers, gastric tissue, pulmonary carcinoid, and SCLC (Muscarella et al., 2021). The specificity and sensitivity of ProGRP for lung cancer were 93.2% and 78.5%, respectively (Aoran et al., 2019). Anti‐GABABR encephalitis is not a completely curable autoimmune disease, and a considerable number of patients have a poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics and elevated ProGRP and positive oligoclonal bands of 13 Chinese cases with anti‐GABABR encephalitis

Wang

Wei

et al. 2021

Intl J of Devlp Neuroscience

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Objective To improve the clinical understanding of anti‐gamma‐aminobutyric‐acid B receptor encephalitis (anti‐GABABR encephalitis) by analyzing 13 cases. Methods We retrospectively studied demographic and clinical features including clinical symptoms, serum/cerebrospinal fluid (CSF) laboratory findings (including antibody test), brain magnetic resonance imaging (MRI), electroencephalogram (EEG), treatment plan, and treatment effect for 13 patients with a definitive diagnosis of anti‐GABABR encephalitis. Results Seven patients (53.8%, 7/13) were complicated with lung cancer. Epileptic seizures were the most common symptoms at onset in 11 patients (84.6%, 11/13). All patients had seizures in the course of the disease. Abnormalities in craniocerebral MRI examination, including hippocampus, occipital lobe, insular lobe, were found in six of nine tested patients, and EEG abnormalities were found in seven out of nine tested patients. Elevated pro‐gastrin releasing peptide (ProGRP) levels were found in 70% of patients with a median value of 490.10 pg/ml; and CSF oligoclonal bands were positive for 4 of 10 tested cases. However, there were no significant differences in modified Rankin Scale (mRS) between the ProGRP or CSF oligoclonal band positive and negative groups at admission and follow‐up (p > .05). The value between SCLC and non‐SCLC subgroup was significantly different (p < .05). Ten patients received immunotherapy (three patients refused treatment). After immunotherapy, the frequency of seizures was significantly reduced. There was a significant difference in mRS between admission and after treatment (p < .05). The average survival time after onset was 27.7 months. Conclusions Epilepsy is the most common clinical manifestation of Anti‐GABABR encephalitis. The prognosis of anti‐GABABR encephalitis is poor. Section of anti‐GABABR encephalitis patients have higher level of serum ProGRP and positive GSF oligoclonal bands. Elevated ProGRP or positive CSF oligoclonal bands with classic clinical features can potentially help to improve early recognition of anti‐GABABR encephalitis.

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Section: Discussionmentioning

confidence: 99%

Clinical characteristics and elevated ProGRP and positive oligoclonal bands of 13 Chinese cases with anti‐GABABR encephalitis

Wang

Wei

et al. 2021

Intl J of Devlp Neuroscience

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“…While SCLC cells display features of neuroendocrine cells, the gene expression programs in metastatic SCLC include not only genes normally expressed in pulmonary neuroendocrine cells but also those expressed in neurons (Carney et al, 1982; Cutz, 1982; Broers et al, 1987; Anderson et al, 1988). Higher levels of the neuronal markers such as NSE (neuron-specific enolase) correlate with shorter survival and more metastatic disease in SCLC patients (Carney et al, 1982; van Zandwijk et al, 1992; Dong et al, 2019). Broad neuronal gene expression programs are enriched in metastases from mouse models of SCLC, however, whether SCLC cells actually gain neuronal characteristics and whether neuronal features are key regulators of metastatic ability has not been previously characterized (Denny et al, 2016; Wu et al, 2016; Yang et al, 2018; Böttger et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Axon-like protrusions promote small cell lung cancer migration and metastasis

Yang

Cai

et al. 2019

eLife

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Metastasis is the main cause of death in cancer patients but remains a poorly understood process. Small cell lung cancer (SCLC) is one of the most lethal and most metastatic cancer types. SCLC cells normally express neuroendocrine and neuronal gene programs but accumulating evidence indicates that these cancer cells become relatively more neuronal and less neuroendocrine as they gain the ability to metastasize. Here we show that mouse and human SCLC cells in culture and in vivo can grow cellular protrusions that resemble axons. The formation of these protrusions is controlled by multiple neuronal factors implicated in axonogenesis, axon guidance, and neuroblast migration. Disruption of these axon-like protrusions impairs cell migration in culture and inhibits metastatic ability in vivo. The co-option of developmental neuronal programs is a novel molecular and cellular mechanism that contributes to the high metastatic ability of SCLC.

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“…While SCLC cells display features of neuroendocrine cells, the gene expression programs in metastatic SCLC include not only genes normally expressed in pulmonary neuroendocrine cells but also those expressed in neurons (Carney et al , 1982, Cutz, 1982, Broers et al , 1987, Anderson et al , 1988). Higher levels of the neuronal markers such as NSE (neuron-specific enolase) correlate with shorter survival and more metastatic disease in SCLC patients (Carney et al , 1982, Dong et al , 2019, van Zandwijk et al , 1992). Broad neuronal gene expression programs are enriched in metastases from mouse models of SCLC, however, whether SCLC cells actually gain neuronal characteristics and whether neuronal features are key regulators of metastatic ability has not been previously characterized (Denny et al , 2016, Wu et al , 2016, Yang et al , 2018, Böttger et al , 2019).…”

Section: Introductionmentioning

confidence: 99%

Axon-like protrusions promote small cell lung cancer migration and metastasis

Yang

Cai

et al. 2019

Preprint

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14Metastasis is the main cause of death in cancer patients but remains a poorly understood 15 process. Small cell lung cancer (SCLC) is one of the most lethal and most metastatic types of 16 human cancer. SCLC cells normally express neuroendocrine and neuronal gene programs but 17 accumulating evidence indicates that these cancer cells become relatively more neuronal and less 18 neuroendocrine as they gain the ability to metastasize. Here we show that mouse and human 19 SCLC cells in culture and in vivo can grow cellular protrusions that resemble axons. The 20 formation of these protrusions is controlled by multiple neuronal factors implicated in 21 axonogenesis, axon guidance, and neuroblast migration. Disruption of these axon-like 22 protrusions impairs cell migration in culture and inhibits metastatic ability in vivo. The co-option 23 of developmental neuronal programs is a novel molecular and cellular mechanism that 24 contributes to the high metastatic ability of SCLC. 25 65 cells that have transitioned to a more neuronal cell state. 66 5 68 To investigate SCLC migration, we developed an assay in which SCLC cells, which 69 classically grow in culture as floating spheres or aggregates, are grown as a monolayer under 70 Matrigel ((Denny et al., 2016) and Methods). Unexpectedly, we noticed that cells from some 71 SCLC cell lines (N2N1G, 16T, 6PF) derived from the Rb f/f ;p53 f/f (DKO) and Rb f/f ;p53 f/f ;p130 f/f 72 (TKO) genetically engineered mouse models form long cellular protrusions into cell-free spaces 73 ( Figure 1A-B). To determine whether these structures specifically project into cell-free areas or 74 they also exist within monolayers, we cultured a minor fraction of fluorescently-labeled, RESULTS 67 SCLC cells can form long cellular protrusions in culture and in vivo 75GFP positive SCLC cells with control SCLC cells. We found that SCLC cells also form protrusions 76 when they are in close contact with surrounding cancer cells (Figure S1A). Similar mixing 77 experiments performed in subcutaneous allografts also documented the growth of protrusions by 78 SCLC cells in vivo (Figure 1C-D). Finally, similar structures also extend from SCLC micro-79 metastases in the liver in the autochthonous TKO mouse model and after intravenous 80 transplantations of SCLC cells (Figure S1B-C). 81Human SCLC patient-derived xenografts (PDXs) recapitulate many important features of the 82 human disease (e.g. (Gardner et al., 2017, Saunders et al., 2015). To label rare cancer cells 83 within human SCLC PDXs and identify whether they had protrusions in unperturbed tumors, we 84 used DiI tracing. DiI is a lipophilic dye that diffuses within cell membranes and has been widely 85 employed to label projections from individual neurons (Heilingoetter and Jensen, 2016, Mufson 86 et al., 1990). Protrusions from SCLC cells were easily identifiable in two out of three PDX 87 models ( Figure 1E-F). In the 2D monolayer culture system, not all human SCLC cell lines 88 formed protrusions, but NCI-H446 cells formed long protru...

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Diagnostic value of ProGRP for small cell lung cancer in different stages

Cited by 21 publications

References 31 publications

Clinical characteristics and elevated ProGRP and positive oligoclonal bands of 13 Chinese cases with anti‐GABABR encephalitis

Clinical characteristics and elevated ProGRP and positive oligoclonal bands of 13 Chinese cases with anti‐GABABR encephalitis

Axon-like protrusions promote small cell lung cancer migration and metastasis

Axon-like protrusions promote small cell lung cancer migration and metastasis

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